WASHINGTON -- After evaluating the pros and cons of conducting a large-scale clinical study of testosterone therapy to treat age-related conditions in men 65 and older, an expert committee of the Institute of Medicine of the National Academies recommended going forward with trials, but only with a limited group of participants and in a stepwise fashion. Initial studies should focus on determining the efficacy of testosterone therapy in older men and the nature and extent of the potential benefits. A large-scale trial to determine long-term risks and effectiveness should be undertaken only if clinically significant benefits are demonstrated in the initial, shorter studies. The studies should involve only older men who have been diagnosed with low testosterone levels and at least one symptom that might be remedied by the therapy, and who are not at high risk for developing prostate cancer, says the committee's report.

Testosterone therapy products have been approved by the U.S. Food and Drug Administration for treating a limited number of conditions, particularly hypogonadism, a clinical condition marked by -- but not defined solely by -- inadequate testosterone production. Hypogonadism occurs in men of various ages, and most clinical studies of the therapy so far have been in younger hypogonadal men. The rapidly growing use of testosterone therapy among men seeking to counter the effects of aging has outpaced the scientific evidence about the therapy's benefits and risks for users -- particularly its possible effects on the prostate, the report notes.

"There is still much we don't know about normal levels of testosterone at different ages, how decreased testosterone levels affect men's health, and whether testosterone therapy might increase the risk of prostate cancer," said committee chair Dan Blazer, professor of psychiatry and behavioral sciences, Duke University Medical Center, Durham, N.C. "There have been only 31 small placebo-controlled studies of testosterone therapy in men ages 65 and older, and just one lasted longer than a year. Recent experience with the Women's Health Initiative -- which studied hormone therapy in postmenopausal women for many years -- underscores the importance of approaching future studies of testosterone therapy thoughtfully and carefully. We have laid out what we believe to be the most prudent course for collecting the data needed to determine if testosterone therapy is an effective and safe treatment option for older men."

Because little is known about the benefits of testosterone therapy and because the number of study participants and amount of time required to assess the therapy's benefits are far less than those needed to assess its risks, resources should be targeted first at firmly establishing the efficacy of testosterone therapy for older males, the report says. The committee estimated that several hundred older men would need to be monitored for one to two years to determine whether testosterone is effective in treating specific health conditions. If clear efficacy is demonstrated in the initial studies, then a large-scale trial involving several thousand men followed over a longer time frame would be warranted, the report says. The limited preliminary evidence currently available suggests that testosterone therapy may have potential benefit for older men in terms of improving strength, sexual function, cognitive function, and general well-being, the committee said.

To minimize study participants' exposure to possible harm, men who are at high risk for developing prostate cancer or who are being treated for benign prostatic hyperplasia should be excluded. All participants should be monitored regularly for changes in prostate-specific antigen levels or in the results of digital rectal examinations.

Given the size and projected growth of the aging male population, it is important to determine the benefits and hazards of this increasingly popular therapy, the report says. The U.S. Census Bureau counted more than 14.7 million American men ages 65 and older in 2002, and projects that this population will reach almost 17 million by 2010. More than 1.75 million prescriptions for testosterone therapy products were written in 2002, approximately a 30 percent jump from the number written in 2001, and a 170 percent increase from 1999. While the majority of testosterone use is by men younger than 65, the number of older men using it is rising as well. The committee was asked to focus specifically on research to determine the therapy's efficacy and risks for men 65 or older.

Studies of older men could shed light on the possible benefits of testosterone therapy for middle-aged men as well, the report notes. However, the studies may not be very informative about the risks for these younger men. Because prostate cancer is a slow-growing and often latent disease, and because the death rate is lower in those under 65, clinical trials to assess the risks for this population would have to be much larger and last many more years than those focused on older men.

The committee found no compelling evidence of major adverse side effects resulting from testosterone therapy, but the evidence is inadequate to document safety, the report says. "Until the efficacy and safety of testosterone therapy in older men is firmly established, we believe that its use is appropriate only for those conditions approved by the FDA, and that it is inappropriate for wide-scale use to prevent possible future disease or to enhance strength or mood in otherwise healthy older men," Blazer said. However, the committee did not examine whether restrictions are needed on use of the therapy in treating conditions other than those for which it has been approved.

The study was sponsored by the National Institute on Aging and the National Cancer Institute. The Institute of Medicine is a private, nonprofit institution that provides health policy advice under a congressional charter granted to the National Academy of Sciences. A committee roster follows.

Testosterone and Aging: Clinical Research Directions is available on the Internet at http://www.nap.edu. Copies of the report will be available for purchase early next year from the National Academies Press; tel. 202-334-3313 or 1-800-624-6242. Reporters may obtain a pre-publication copy from the Office of News and Public Information (contacts listed above).